The AIMilano variant is the first molecular abnormality described in a human apolipoprotein. Subjects with this metabolic condition show increased triglyceridemia and markedly reduced high density lipoprotein (HDL) cholesterol levels. None of these subjects, however (the age range spanning up to 81) has any sign or symptom of the atherosclerotic disease. Preliminary data indicate that one aminoacid error (a cys-arg replacement in apo AI) may be the cause of the whole condition, also leading to accelerated apo AI catabolism, and to enhanced liver uptake of the modified apoprotein. The origin of the variant gene having been located in an Italian village, genetic studies have been planned in order to characterize the mode of transmission of the defect and eventual other accompanying traits. At least 500 residents of the village, where the AIMilano family originates, will be sampled, in an effort to identify as many as possible family nuclei with the molecular defect. Complete genetic pedigrees of the affected families will be designed in an effort to: 1) investigate the segregation of the AIMilano phenotype; 2) statistically verify its adherence to a Mendelian mode of inheritance; 3) study specific genetic markers, immunohematological, enzymatic and chromosomal to establish a possible linkage of the AIMilano trait. In the course of these genetic studies, it will be possible to further define the association between reduced HDL cholesterol, hypertriglyceridemia and absence of atherosclerotic disease in the affected subjects. Moreover, the association of any other pathological condition will be established. The availability of a more numerous group of affected subjects will facilitate further, more detailed investigations on the variety of biochemical problems correlated with the AIMilano abnormality.